crossing96/oncoscreening huggingface dataset:
Diagnostic predictive value of the Bladder EpiCheck test in the follow-up of patients with non-muscle-invasive bladder cancer.	BACKGROUND: The objective of this study was to evaluate the diagnostic accuracy of the Bladder EpiCheck test in the follow-up of patients with non-muscle-invasive bladder cancer (NMIBC) and to compare it with the accuracy of urinary cytology, cystoscopy, and/or histology. METHODS: In total, 243 patients were enrolled in the current study. Patients were evaluated by voided urine cytology, by the Bladder EpiCheck test, and by white-light cystoscopy. RESULTS: Overall sensitivity was 33.3% for cytology, 62.3% for Bladder EpiCheck, and 66.7% for the 2 tests combined. The sensitivity of cytology increased from 7.7% in low-grade (LG) tumors to 66.6% in high-grade (HG) tumors; whereas, for the Bladder EpiCheck test, the sensitivity was 46.1% in LG tumors and 83.3% in HG tumors. Combined cytology and Bladder EpiCheck testing yielded an overall sensitivity of 56.4% for LG tumors and 90% for HG tumors. Overall specificity was 98.6% for cytology, 86.3% for Bladder EpiCheck, and 85.6% for the 2 tests combined. The positive predictive value was 92% for cytology and 68.2% for Bladder EpiCheck. For the 2 tests combined, it was 68.6%. The negative predictive value was similar for the 2 tests: 75.8% for cytology, 82.9% for Bladder EpiCheck, and 84.5% for the 2 tests combined. CONCLUSIONS: The sensitivity of the Bladder EpiCheck test was significantly higher than that of cytology. The test performed very well in terms of specificity but could not reach the high value of cytology. The positive predictive value was higher for Bladder EpiCheck, whereas the negative predictive value was approximately the same for both tests.	bladder
Single-centre Experience of Patients with Metastatic Urothelial Cancer Treated with Chemotherapy Following Immune Checkpoint Inhibition.	There are few data on outcomes for patients with metastatic urothelial carcinoma (MUC) who receive chemotherapy (CT) after progression on immune checkpoint inhibitors (ICIs). We carried out a retrospective single-centre analysis of MUC patients who progressed after ICI and then received CT. Patients fell into two groups: CT-naive (no prior-CT) and CT-pretreated (platinum-based CT followed by ICI on progression). The response rate (RR), progression-free survival (PFS), and duration of response (DOR) were assessed. A total of 29 patients received CT following progression on ICI. The median follow-up was 17.0mo (interquartile range 9.1-20.5mo). In the CT-naive group (n=17), 53% had a partial response, 18% had stable disease, and 29% had progressive disease. In the CT-pretreated group (n=12) 17% had a partial response, 67% had stable disease, and 16% had progressive disease. The median PFS was 6.4mo (95% confidence interval [CI] 3.8-9.1) in the CT-naive and 4.4mo (95% CI 1.5-7.3) in the CT-pretreated group. The median DOR was 8.1mo (range 5.1-11.1) among the ten patients with a response to CT after ICI in both groups. Some 38% of patients in the CT-naive and 17% in the CT-pretreated group had dose reductions on post-ICI CT. CT and ICI can be sequenced after previous chemotherapy exposure, although this does not induce long-term durable remissions in most patients. PATIENT SUMMARY: We looked at outcomes for patients with metastatic bladder cancer who received chemotherapy after the cancer got worse while on immunotherapy. We found that patients can be safely treated with further chemotherapy. However, the positive effects of chemotherapy will not be durable in the majority of patients.	bladder
Predictive factors for progression of patients with carcinoma in situ of the bladder at long-term follow-up: pure versus non-pure CIS.	BACKGROUND: The aim of this study was to identify the predictive factors for progression defined as any event that shifted the management of the disease from a bladder sparing approach, by comparing patients with pure versus non-pure carcinoma in situ (CIS) of the bladder. METHODS: A retrospective analysis was carried out in consecutive patients affected by newly-diagnosed pure CIS and non-pure CIS (excluding cases with concomitant muscle invasive cancer). All patients were enrolled a in our institution from 1998 to 2010. Data was prospectively collected. Main end point was progression-free survival. RESULTS: Overall, 149 patients with CIS were identified for the analysis. A total of 98 patients had pure CIS (66%). Median follow-up was 103 months (range: 40-206 months). Progression occurred in 29 patients (19%). A total of 30 patients died during the follow-up (20%). In 13 cases (9%), the death was cancer specific. Progression-free survival estimate was 181 months (95% CI: 169-193 months) and 154 months (95% CI: 133-176 months) respectively for pure and non-pure CIS population (P=0.03). Among examined variables (age, gender, symptoms, smoking habit, ASA score, number of bacillus Calmette-Guérin [BCG] instillations), multivariate analysis disclosed that only CIS type was an independent predictor of progression (P=0.03) with a relative risk of 0.37 in favor of pure CIS. CONCLUSIONS: Pure and non-pure CIS are efficiently treated by BCG therapy combined with trans-urethral resection and/or radical cystectomy, with relatively low rate of progression. CIS type was the only significant predictor of progression.	bladder
Association between AXIN1 Gene Polymorphisms and Bladder Cancer in Chinese Han Population.	BACKGROUND: Previous evidence has indicated that the reduction of axis inhibition protein 1 (AXIN1) expression is related with the poor differentiation of non-small-cell lung cancer (NSCLC). However, the potential association between AXIN1 and bladder cancer (BC) is unknown. We aimed to initially explore the relevance of AXIN1 gene polymorphisms (rs12921862 C/A, rs1805105 T/C, and rs370681 C/T) and BC. METHODS: Three hundred and sixteen BC patients and 419 healthy controls had been enrolled. Polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) method was used for genotyping three tag single-nucleotide polymorphisms (SNPs) of AXIN1. The SNPstats online analysis software and SPSS software were used for statistical analysis. RESULTS: Our data revealed that three tag SNPs were associated with an increased risk of BC (rs12921862: P < 0.001, OR (95%CI) = 4.61 (3.13-6.81); rs1805105: P = 0.046, OR (95%CI) = 1.35 (1.00-1.82); and rs370681: P = 0.004, OR (95%CI) = 1.56 (1.15-2.10)). For rs12921862, A allele was an independently protective factor which correlated with a better prognosis in non-muscle-invasive bladder cancer (NMIBC) patients (P = 0.03, OR (95%CI) = 0.10 (0.01-0.84)). Stratification analysis demonstrated that rs370681 polymorphism was related with high-grade bladder cancer (P = 0.04, OR (95%CI) = 1.85 (1.04-3.23)). CONCLUSION: The AXIN1 gene polymorphisms might implicate in BC risk, and rs12921862 could be a potential forecasting factor for prognosis of BC patients.	bladder
Exosomes containing ErbB2/CRK induce vascular growth in premetastatic niches and promote metastasis of bladder cancer.	Locally advanced and metastatic invasive bladder cancer (BC) has a poor prognosis, and no advanced therapies beyond cisplatin-based combination chemotherapy have been developed. Therefore, it is an urgent issue to elucidate the underlying mechanisms of tumor progression and metastasis of invasive BC for the development of new therapeutic strategies. Here, we clarified a novel role of exosomes containing ErbB2 and CRK in a formation of premetastatic niches and subsequent metastases. CRK adaptors were overexpressed in invasive UM-UC-3 BC cells. In an orthotopic xenograft model, metastases to lung, liver, and bone of UM-UC-3 cells were completely abolished by CRK elimination. Mass spectrometry analysis identified that ErbB2 was contained in UM-UC-3-derived exosomes in a CRK-dependent manner; the exosomes significantly increased proliferation and invasion properties of low-grade 5637 BC cells and HUVECs through FAK and PI3K/AKT signaling pathways. In athymic mice educated with UM-UC-3-derived exosomes, i.v. implanted UM-UC-3 cells were trapped with surrounding PKH67-labeled exosomes in lung and led to development of lung metastasis with disordered vascular proliferation. In contrast, exosomes derived from CRK-depleted BC cells failed to induce these malignant features. Taken together, we showed that CRK adaptors elevated the expression of ErbB2/3 in BC cells, and these tyrosine kinase/adaptor units were transferred from host BC cells to metastatic recipient cells by exosomes, leading to vascular leakiness and proliferation and contributing to the formation of distant metastasis. Thus, CRK intervention with ErbB2/3 blockade might be a potent therapeutic strategy for patients with ErbB2 overexpressing advanced and metastatic BC.	bladder
Circular RNA Cdr1as sensitizes bladder cancer to cisplatin by upregulating APAF1 expression through miR-1270 inhibition.	Circular RNAs (circRNAs) have recently emerged as essential regulators in carcinogenesis and cancer progression. Previous studies have shown that Cdr1as functions as a microRNA (miRNA) sponge in various cancer types. However, the role of Cdr1as in cisplatin chemosensitivity in bladder cancer remains unclear. Here, we used real-time PCR to examine miRNA and gene expression in bladder cancer tissues and cell lines. The abilities of Cdr1as and its downstream regulatory molecules to induce apoptosis and promote cisplatin-induced chemosensitivity of bladder cancer cells were determined by flow cytometry and cell counting kit. Bioinformatic analysis was utilized to predict potential miRNA target sites, and biotin-coupled miRNA capture, biotin-coupled probe pull-down assay, and RNA fluorescent in situ hybridization were used to study the interaction between Cdr1as and target miRNAs. Dual-luciferase reporter assay was also used to validate the target genes of miRNAs. The expression level of apoptotic protease-activating factor 1 (APAF1) in bladder cancer cells was identified via western blot. Finally, the sensitivity of Cdr1as to cisplatin chemotherapy in nude mice xenografts was evaluated in terms of the size, volume of tumors, and the survival of mice. We report that Cdr1as induced the apoptosis and enhanced the cisplatin chemosensitivity of bladder cancer cells both in vitro and in vivo. Silencing of APAF1 reduced the sensitivity of bladder cancer cells to cisplatin chemotherapy. Furthermore, Cdr1as could directly sponge miR-1270 and abolish its effect on APAF1. Our study verified that Cdr1as exerts a cisplatin-chemosensitization effect on bladder cancer cells through the Cdr1as/miR-1270/APAF1 axis. This newly identified axis may be a potential therapeutic target for bladder cancer patients.	bladder
Jarid2 enhances the progression of bladder cancer through regulating PTEN/AKT signaling.	AIMS: Jumonji AT-rich interactive domain 2 (Jarid2) is an interacting component of PRC2 which catalyzes methylation of H3K27 (H3K27me3) and causes the downregulation of PTEN. In the present study, we aimed to explore whether Jarid2 could interact with H3K27me3 to regulate PTEN expression in bladder cancer. MAIN METHODS: Jarid2 expression in bladder cancer tissues and cells were determined by western blotting and RT-PCR. CCK-8, flow cytometry, transwell chamber and in vivo xenograft assays were performed to assess cell growth, apoptosis, migration and tumorigenesis, respectively. Chromatin immunoprecipitation (ChIP) assay was used to assess the methylation of PTEN. KEY FINDINGS: Jarid2 expression was increased in bladder cancer tissues and cells. Downregulation of Jarid2 with shRNA transfection obviously inhibited the proliferation, migration and tumorigenesis of bladder cancer T24 and HT-1376 cells and induced cell apoptosis. Jarid2 downregulation decreased the expression of p-AKT and increased PTEN expression. Besides, Jarid2 down-regulation repressed the epithelial-mesenchymal transition (EMT), whereas knockdown of PTEN impaired this effect. Moreover, upregulation of Jarid2 increased the combination of PTEN promoter and H3K27me3, and 5-aza-CdR rescued it. Meanwhile, 5-aza-CdR administration abolished Jarid2 roles in the promotion of EMT process and AKT activation, as well as the reduction of PTEN expression. SIGNIFICANCE: Overall, the present study elaborated that Jarid2 facilitated the progression of bladder cancer through H3K27me3-mediated PTEN downregulation and AKT activation, which might provide a new mechanism for Jarid2 in promoting bladder cancer progression.	bladder
Robot-assisted radical cystectomy with totally intracorporeal urinary diversion: surgical and early functional outcomes through the learning curve in a single high-volume center.	The aim of the study is to report surgical and early functional outcomes of first 100 patients undergoing robot-assisted radical cystectomy (RARC) with totally intracorporeal urinary diversion (ICUD) in a single center. The main surgeon (A.P.) attended a modular training program at a referring center mentored by a worldwide-recognized robotic surgeon (P.W.). The program consisted of: (a) 10 h of theoretical lessons; (b) video session (c) step-by-step in vivo modular training. Each procedure was performed as taught, without any technique variation. Demographics, intra-operative data and post-operative complications, along with early functional outcomes, were recorded for each patient. We retrospectively evaluated the first consecutive 100 patients submitted to RARC with totally ICUD from July 2015 to December 2018. Median age at surgery was 69 years (IQR 60-74). 52 (52%), 32 (32%), and 17 (17%) patients received orthotopic neobladder, ileal conduit and uretero-cutaneostomy, respectively. Median operative time was 410 min. A median number of lymph nodes retrieved were 27 and median estimated blood loss was 240 mL with median hospitalization time of 7 days. All procedures were completed successfully without open conversion. A statistically significant improvement was found in the late (30-90 post-operative days) post-operative complications (p = 0.02) and operative time for urinary derivation. At multivariate logistic regression model ASA score ≥ 3 (OR = 4.2, p = 0.002) and number of lymph nodes retrieved (OR = 1.16, p = 0.02) were found to be predictors of 90-day complications. An adequate modular training is paramount to obtain successful results and reduce the learning curve of RARC, as demonstrated by our experience.	bladder
Evaluation of the Fluorescence In Situ Hybridization Test to Predict Recurrence and/or Progression of Disease after bacillus Calmette-Guérin for Primary High Grade Nonmuscle Invasive Bladder Cancer: Results from a Prospective Multicenter Trial.	PURPOSE: Single center studies have shown that positive UroVysion® fluorescence in situ hybridization results were associated with recurrence of nonmuscle invasive bladder cancer treated with intravesical bacillus Calmette-Guérin. Our goal was to validate these findings. MATERIALS AND METHODS: We performed a prospective, multicenter diagnostic trial to determine whether the fluorescence in situ hybridization test could predict recurrence or progression in patients with primary high grade nonmuscle invasive bladder cancer who were scheduled to receive bacillus Calmette-Guérin. Fluorescence in situ hybridization testing was performed prior to the first bacillus Calmette-Guérin instillation, prior to the sixth instillation and at 3-month cystoscopy. The performance of fluorescence in situ hybridization was evaluated. RESULTS: A total of 150 patients were enrolled in analysis, including 68 with Ta disease, 41 with T1 disease, 26 with carcinoma in situ alone and 15 with papillary carcinoma plus carcinoma in situ. At 9 months of followup there were 46 events, including 37 recurrences and 9 progressions. For events with positive fluorescence in situ hybridization findings the HR was 2.59 (95% CI 1.42-4.73) for the baseline test, 1.94 (95% CI 1.04-3.59) for the 6-week test and 3.22 (95% CI 1.65-6.27) at 3 months. Patients with positive results at baseline, 6 weeks and 3 months had events 55% of the time and patients with negative results at each time point had no event 76% of the time. CONCLUSIONS: The study validated that a positive UroVysion fluorescence in situ hybridization test was associated with a 3.3-fold increased risk of recurrence. The test may be useful to risk stratify patients entering clinical trials in whom induction therapy fails. However, using the test to change management decisions is limited due to the discordance between results and outcomes as well as the variance of tests results with time.	bladder
Understanding the predictive value of continuous markers for censored survival data using a likelihood ratio approach.	"BACKGROUND: The likelihood ratio function (LR), the ratio of conditional probabilities of obtaining a specific marker value among those with the event of interest over those without, provides an easily interpretable way to quantify the update of the risk prediction due to the knowledge of the marker value. The LR has been explored for both binary and continuous markers for binary events (e.g., diseased or not), however the use of the LR in censored data has not been fully explored. METHODS: We extend the concept of LR to a time-dependent LR (TD-LR) for survival outcomes that are subject to censoring. Estimation for the TD-LR is done using Kaplan-Meier estimation and a univariate Cox proportional hazards (PH) model. A ""scale invariant"" approach based on marker quantiles is provided to allow comparison of predictive values between markers with different scales. Relationships to time-dependent receiver-operator characteristic (ROC) curves, area under the curve (AUC), and optimal cut-off values are considered. RESULTS: The proposed methods were applied to data from a bladder cancer clinical trial to determine whether the neutrophil-to-lymphocyte ratio (NLR) is a valuable biomarker for predicting overall survival following surgery or combined chemotherapy and surgery. The TD-LR method yielded results consistent with the original findings while providing an easily interpretable three-dimensional surface display of how NLR related to the likelihood of event in the trial data. CONCLUSIONS: The TD-LR provides a more nuanced understanding of the relationship between continuous markers and the likelihood of events in censored survival data. This method also allows more straightforward communication with a clinical audience through graphical presentation."	bladder
Long non-coding RNAs in genitourinary malignancies: a whole new world.	Long non-coding RNAs (lncRNAs) are regulators of cellular machinery that are commonly dysregulated in genitourinary malignancies. Accordingly, the investigation of lncRNAs is improving our understanding of genitourinary cancers, from development to progression and dissemination. lncRNAs are involved in major oncogenic events in genitourinary malignancies, including androgen receptor (AR) signalling in prostate cancer, hypoxia-inducible factor (HIF) pathway activation in renal cell carcinoma and invasiveness in bladder cancer, as well as multiple other proliferation and survival mechanisms. In line with their putative oncogenic roles, new lncRNA-based classifications are emerging as potent predictors of prognosis. In clinical practice, detection of oncogenic lncRNAs in serum or urine might enable early cancer detection, and lncRNAs might also be promising therapeutic targets for patients with genitourinary cancer. Furthermore, as predictors of sensitivity to anticancer treatments, lncRNAs could be integrated into future precision medicine strategies. Overall, lncRNAs are promising new candidates for molecular studies and for discovery of innovative biomarkers and are putative therapeutic targets in genitourinary oncology.	bladder
Androgen Suppression Therapy Is Associated with Lower Recurrence of Non-muscle-invasive Bladder Cancer.	BACKGROUND: The challenge of managing non-muscle-invasive bladder cancer (NMIBC) is its high recurrence rate. Clinical investigations have begun to explore the role of androgen suppression as an adjunct to bladder cancer (BC) treatment. OBJECTIVE: To examine the effect of androgen suppression therapy (AST) on recurrence and progression rate of risk-stratified NMIBC. DESIGN, SETTING, AND PARTICIPANTS: Male patients with NMIBC were identified retrospectively from a US institutional database between 2001 and 2017. AST included 5α-reductase inhibitor, gonadotropin-releasing hormone agonist, and antiandrogen. Patients who were exposed to AST prior to documented recurrence/progression were included in the treatment arm. BC was risk stratified to investigate the differential response to AST. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: Hazard ratios (HRs) for NMIBC recurrence and progression were estimated using Cox proportional hazards multivariate regression models with stepwise method. Recurrence-free survival (RFS) and progression-free survival (PFS) were compared between groups with and without AST. RESULTS AND LIMITATIONS: We identified a total of 274 males with a median follow-up period of 3.1 yr (interquartile range [IQR] 1.5-5.2). Thirty-six patients were exposed to AST with a median duration of 1.7 yr (IQR 0.7-2.6). AST was associated with a lower risk of recurrence (HR 0.53, 95% confidence interval 0.30-0.88) as well as improved RFS (p =  0.014). However, no significant reduction of progression or improvement of PFS (p =  0.23) was found with AST. After risk stratification, all five patients who progressed in the AST cohort had high-risk disease on initial transurethral resection (TUR), whereas no patients with low/intermediate-risk disease progressed on AST. Limitations of the study include nonstandardized initiation of AST in relation to initial TUR, lack of androgen level quantification, and small sample size in the treatment arm. CONCLUSIONS: In this retrospective, single-institution study, AST was associated with a lower risk of recurrence in NMIBC. No significant association between AST and progression was found. Further investigation is warranted to define the role of AST as an adjunctive therapy for NMIBC. PATIENT SUMMARY: Non-muscle-invasive bladder cancer is a highly recurrent disease that often requires patients to undergo repeated surgical treatments. This single-institution report suggests that medical suppression of androgen may be a potential preventive therapy to reduce recurrence in certain patients.	bladder
Human urothelial bladder cancer generates a clonal immune response: The results of T-cell receptor sequencing.	BACKGROUND: High T-cell receptor (TCR) repertoire clonality is associated with clinical response to immune checkpoint blockade in bladder cancer. OBJECTIVE: To determine if TCR repertoire is more clonal in tumors than in benign inflammation. METHODS: We prospectively identified 12 patients with bladder lesions undergoing transurethral resection. Specimens were collected at time of transurethral resection and stored at -80C. DNA was extracted and high throughput DNA sequencing of the CDR3 region of the TCR beta chain using the immunoSEQ assay (Adaptive Biotechnologies) was performed. T-cell fraction, clonal dominance, and maximum frequency of TCR clone were assessed. RESULTS: Of the 12 bladder lesions resected, 3 of 12 were cT0, 3 of 12 were cTa, 3 of 12 were cT1, and 3 of 12 were cT2 or greater. The median number of T cells in urothelial carcinoma specimens (UC+) and benign (UC-) specimens was 5,569 and 25,872, respectively. The number of unique TCRs sequenced in UC+ and UC- specimens was 3,069 and 9,680, respectively. The median tumor infiltrating lymphocyte percentage in UC+ and UC- specimens was 2% and 12%, respectively. The UC+ specimens demonstrated clonality as evidenced by identification of a specific T-cell clone being present in up to 17% of the total tumor infiltrating lymphocyte pool, in contrast to 2% among UC- specimens. CONCLUSIONS: Primary urothelial tumors contain clonally expanded T-cell populations. These data support the hypothesis that bladder tumors induce an antigen-driven immunogenic host response, in contrast to the benign inflammatory response, which does not appear to demonstrate any T-cell clonal dominance.	bladder